One- versus two-sample fecal immunochemical testing for colorectal cancer screening: a systematic review and meta-analysis of participation, diagnostic performance, and cost-effectiveness

BACKGROUND: Whether collecting one or two fecal samples for immunochemical testing (FIT) optimizes colorectal cancer screening outcomes remains unclear. METHODS: We systematically searched multiple databases until October 2025 for studies directly comparing 1-FIT and 2-FIT strategies. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated for dichotomous outcomes. RESULTS: Five studies (n = 45,888) and three economic evaluations were included. Participation was higher with 1-FIT (RR = 1.05, P < 0.0001), while 2-FIT had a higher positivity rate (RR = 0.65, P < 0.0001). Although 2-FIT detected more CRC (RR = 0.62, P = 0.02), advanced neoplasia and advanced adenoma detection were similar. The 2-FIT strategy had higher sensitivity (RR = 0.64, P = 0.04) but lower specificity (RR = 1.70, P < 0.001) than 1-FIT. A pivotal finding was that the 1-FIT strategy demonstrated a superior positive predictive value (PPV) for both advanced neoplasia (RR = 1.21, P = 0.004) and advanced adenoma (RR = 1.41, P < 0.0001), which translated into a substantially lower demand for colonoscopy (RR = 0.64, P < 0.0001) Economic evaluations consistently favored 1-FIT across different healthcare systems. CONCLUSION: Although the 2-FIT strategy improves test sensitivity, it fails to enhance advanced neoplasia detection while substantially increasing colonoscopy demand due to its reduced positive predictive value. In contrast, the 1-FIT strategy preserves screening efficacy with superior participation rates, resource utilization, and cost-effectiveness. We recommend 1-FIT as the preferred strategy in settings with constrained colonoscopy resources, while reserving 2-FIT for resource-abundant environments where maximizing sensitivity justifies the additional economic and operational costs (Scheme 1). TRIAL REGISTRATION: The research protocol was prospectively registered in the PROSPERO registry, bearing the registration identifier CRD420251153202.